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USA: West Nile virus outbreak pattern stymie vaccine work

West Nile virus has been a worry for U.S. public health departments for more than a decade, but the outbreak in 2012 could be on track to be the country’s largest ever. It has already prompted a blitz of warnings to avoid virus-infected mosquitoes, underlined with a caveat: There is no vaccine or treatment for West Nile infection. Researchers say the failure is not for lack of trying.

After the first cases were detected 13 years ago in New York City, a burst of money went into thwarting the then-mysterious disease. The basic science has come a long way since then, but measures to prevent or treat West Nile infection have stalled. One big reason is that the sporadic nature of outbreaks makes it hard to get enough volunteers for trials.

The peak so far for West Nile was 2003: 9,862 cases and 264 deaths were reported to the Centers for Disease Control and Prevention (CDC). In 2012, as of 21 August, CDC had received reports of 1,118 cases and 41 deaths, the highest count ever by the third week in August 2012. About half the cases have been in Texas, where Dallas declared a state of emergency and began aerial spraying. Other hot spots are in Mississippi, Louisiana, South Dakota, and Oklahoma. Given the up to two-week lag between when people become infected and when they become ill, cases will likely keep rising through September, says Lyle Petersen, director of CDC’s division of vector-borne diseases in Colorado.

Although the causes of the outbreak aren’t clear, many experts suspect that hot weather and drought combined to spur an explosion in Culex mosquitoes, the species that spreads West Nile, and a high rate of virus-infected mosquitoes. In addition, a mild winter helps overwintering adult mosquitoes survive. Hot temperatures spur mosquito development and allow the virus to replicate faster inside mosquitoes, notes arbovirologist Laura Kramer of the New York State Department of Health in Albany. And drought favors Culex mosquitoes’ preferred breeding habitat: pools of water rich in organic material, such as in underground drains. Normally, rains flush out such pools. In addition, drought may have forced birds that carry and amplify the virus to move from rural areas to cities to find water, says entomologist William Reisen of the University of California, Davis.

Much of the virus’s transmission cycle is now well-known: “I think we’ve dissected it more than any other mosquito-borne virus that’s been studied,” Kramer says. Researchers also developed fast diagnostic tests for West Nile, including one that has protected the blood supply. However, efforts to develop a licensed vaccine stalled. The National Institute of Allergy and Infectious Diseases (NIAID) poured money into a vaccine made from a weakened backbone of yellow fever virus with two genes for coat proteins swapped for the West Nile version of those genes. The vaccine, developed by Acambis in Cambridge, Massachusetts, made it through a phase II trial that found a single dose was safe and could generate high levels of protective antibodies. “This is a really good vaccine,” says Thomas Monath, former Acambis vice president and now a consultant.

But in 2008, Sanofi Pasteur bought Acambis and suspended the West Nile program. West Nile cases had dropped from 2006 to 2008, and the company decided to focus on other priorities, including a dengue vaccine, says Sanofi spokesperson Susan Watkins. “Unfortunately we have to pick and choose, and it didn’t make the cut.”

Some researchers say market uncertainty may have been a problem, too. “Who’s going to pay for a vaccine? It won’t be cheap,” says virologist Robert Tesh of the University of Texas Medical Branch in Galveston. It might be given only to the elderly, who are most vulnerable to severe disease, and perhaps highly exposed groups such as outdoor workers, says CDC’s Erin Staples. Monath, however, points to new evidence suggesting that West Nile virus can cause kidney damage in younger people. A team at Baylor College of Medicine in Houston, Texas, reported August 2012 in PLoS ONE that in a cohort of 139 people with a mean age of 57 who tested positive for West Nile virus, years later 40% had evidence of kidney disease. “If proven, this creates a completely different set of priorities for a vaccine,” Monath says.

Work on treatments has been delayed for similar reasons. Trials of three drugs—a monoclonal antibody, interferon, and immunoglobin—were halted in part because researchers couldn’t enroll enough trial volunteers, Staples notes. “It’s going to be difficult to do any kind of study with patients in outbreak sites when you don’t know when and where it’s going to occur,” says Patricia Repik of NIAID.

Yet even if treatments were available, they might not be of much help. The virus usually causes only flulike symptoms at first; less than 1% of those infected develop serious neuroinvasive disease. By the time patients reach a hospital, often with meningitis or encephalitis, “the nerve damage is already done,” Tesh says. What’s needed, Repik says, is “almost a home test” so people who get sick could know early on whether they have a West Nile infection. The National Institutes of Health is funding such research as part of $65 million it will spend in 2012 on West Nile and related diseases.

One frustration for West Nile experts is that funding for state labs and CDC’s vector-borne diseases division has dropped off in recent years. Kramer predicts, “This year (2012) may change that.” At the same time, West Nile infections will likely subside in 2013 in the current epidemic areas because so many birds will have become infected and will be immune to the virus, Reisen says.
(Science 8/31/2012)